Tijaabada methylation DNA oo lagu daray taleefannada casriga ah ee baaritaanka hore ee burooyinka iyo baaritaanka leukemia-ga iyadoo sax ah 90.0%!

Ogaanshaha hore ee kansarka ee ku salaysan biopsy dareere ah waa jihada cusub ee ogaanshaha kansarka iyo ogaanshaha ay soo jeedisay Machadka Qaranka ee Kansarka Maraykanka sannadihii u dambeeyay, iyada oo ujeedadu tahay in la ogaado kansarka hore ama xitaa nabarada kansarka. Waxaa si weyn loo isticmaalay sidii biomarker novel ah oo loogu talagalay ogaanshaha hore ee cudurrada malignantiga ah, oo ay ku jiraan kansarka sanbabada, burooyinka caloosha iyo mindhicirka, gliomas iyo burooyinka haweenka.

Soo ifbaxa goobo lagu aqoonsado muuqaalka methylation (Methylscape) biomarkers ayaa awood u leh inay si weyn u wanaajiso baaritaanka hore ee kansarka, taasoo bukaannada gelinaysa heerka ugu horreeya ee la daweyn karo.

Dhowaan, cilmi-baarayaashu waxay soo saareen sahal fudud oo dareen toos ah oo loogu talagalay ogaanshaha muuqaalka muuqaalka methylation oo ku salaysan cysteamine qurxin nanoparticles dahab ah (Cyst/AuNPs) oo ay weheliso biosensor-ku-salaysan casriga ah kaas oo awood u siinaya baadhis degdeg ah oo degdeg ah oo ballaaran oo burooyin ah. Baaritaanka hore ee leukemia-ga waxaa la samayn karaa 15 daqiiqo gudahood ka dib marka DNA laga soo saaro muunada dhiigga, iyadoo sax ahaanta ay tahay 90.0%. Cinwaanka maqaalku waa ogaanshaha degdega ah ee DNA-da kansarka ee ku jira dhiigga bini'aadamka iyadoo la adeegsanayo cysteamine-capped AuNPs iyo mashiinka casriga ah ee karti u leh barashada.

Jaantus 1. Madal dareemi fudud oo degdeg ah oo loogu talagalay baadhista kansarka iyada oo loo marayo qaybaha Cyst/AuNPs ayaa lagu dhammayn karaa laba tillaabo oo fudud.

Tan waxa lagu muujiyay sawirka 1. Marka hore, xal aqueous ayaa la isticmaalay si loo milo jajabyada DNA-da. Cyst/AuNPs ayaa markaa lagu daray xalka isku dhafan. DNA-da caadiga ah iyo kuwa xun waxay leeyihiin sifooyin methylation oo kala duwan, taasoo keentay jajabyo DNA oo leh qaabab isku-ururin kala duwan. DNA-da caadiga ah waxay isu keentaa si dabacsan oo aakhirka isu geynaysa Cyst/AuNPs, taasoo keenta dabeecadda guduudan ee Cyst/AuNPs, si isbeddelka midabka casaanka ilaa guduudka ah lagu arki karo isha qaawan. Taas bedelkeeda, astaanta methylation ee gaarka ah ee DNA-da kansarka waxay keentaa soo saarista kooxo waaweyn oo jajabyo DNA ah.

Sawirrada taarikada 96-ceelka ah ayaa laga qaaday iyadoo la isticmaalayo kamarad casriga ah. DNA-da kansarka waxa lagu cabiray talefan casriga ah oo ku qalabaysan barashada mashiinka marka loo eego hababka ku salaysan spectroscopy.

Baaritaanka kansarka ee shaybaarada dhiigga dhabta ah

Si loo kordhiyo isticmaalka goobta dareenka, baarayaashu waxay codsadeen dareeme si guul leh u kala soocay DNA-da caadiga ah iyo kansarka sanbabada dhiiga dhabta ah. Qaababka methylation-ka ee goobaha CpG ayaa si epigenetically u habeeya muujinta hidda-socodka. Ku dhowaad dhammaan noocyada kansarka, isbeddellada methylation DNA iyo sidaas muujinta hidda-socodka kor u qaadaya tumourigenesis ayaa lagu arkay beddelka.

Tusaale ahaan kansarrada kale ee la xidhiidha DNA-da methylation, cilmi-baarayaashu waxay isticmaaleen muunadaha dhiigga ee bukaannada leukemia-ga iyo kontaroolada caafimaadka leh si ay u baaraan waxtarka muuqaalka methylation ee kala soocidda kansarka leukaemic. Muuqaalkan methylation biomarker ma aha oo kaliya in uu ka sarreeyo hababka baaritaanka dhiigga ee degdega ah ee hadda jira, laakiin sidoo kale wuxuu muujinayaa suurtogalnimada sii fidinta hore ee ogaanshaha noocyo badan oo kansar ah iyadoo la adeegsanayo baaritaankan fudud oo toosan.

DNA laga soo qaaday muunado dhiig oo laga soo qaaday 31 bukaan oo leukemia ah iyo 12 qof oo caafimaad qaba ayaa la baadhay. sida ku cad goobta sanduuqa ee Jaantuska 2a, nuugista qaraabada ee shaybaarada kansarka (ΔA650/525) way ka hoosaysay tan DNA-da ee shaybaarada caadiga ah. Tani waxay inta badan sabab u ahayd hydrophobicity la xoojiyey taasoo keentay isu geynta cufan ee DNA-da kansarka, taas oo ka hortagtay isu-ururinta Cyst/AuNPs. Natiijo ahaan, nanoparticles-yadan ayaa si buuxda ugu kala firdhiyey lakabyada dibadda ee isku-darka kansarka, taas oo keentay kala firdhisanaan kala duwan oo Cyst/AuNPs ah oo lagu dhajiyay isku-darka DNA-ga caadiga ah iyo kansarka. Curyaaminta ROC ayaa markaa la abuuray iyadoo laga beddelayo heerka ugu hooseeya ee ΔA650/525 ilaa qiimaha ugu sarreeya.

Jaantuska 2.(a) Qiimaha nuugista qaraabada ah ee xalalka cyst/AuNPs oo muujinaya joogitaanka caadiga ah (buluug) iyo kansarka (casaan) dna ee xaaladaha la hagaajiyay

(DA650/525) ee boosaska sanduuqyada; (b) Falanqaynta iyo qiimaynta ROC ee imtixaannada ogaanshaha. (c) Matrix jahawareer oo loogu talagalay ogaanshaha bukaanka caadiga ah iyo kuwa kansarka. (d) Dareenka, gaar ahaan, qiimaha saadaasha togan (PPV), qiimaha saadaasha xun (NPV) iyo saxnaanta habka la sameeyay.

Sida ku cad Jaantuska 2b, aagga hoos yimaada qalooca ROC (AUC = 0.9274) ee loo helay dareenka horumaray ayaa muujiyay dareen sare iyo gaar ahaaneed. Sida laga arki karo goobta sanduuqa, meesha ugu hooseysa ee matalaysa kooxda DNA-da caadiga ah si fiican uma kala soocna meesha ugu sarreysa ee matalaysa kooxda DNA-ga kansarka; Sidaa darteed, dib-u-celinta saadka ayaa loo isticmaalay in lagu kala saaro kooxaha caadiga ah iyo kuwa kansarka. Marka la eego go'an doorsoomayaal madax-bannaan, waxay qiyaastay ixtimaalka ay dhacdo dhacdo, sida kansar ama koox caadi ah. Doorsoomaha ku-tiirsanku wuxuu u dhexeeyaa 0 iyo 1. Natiijadu waa suurtogal. Waxaan go'aansanay suurtagalnimada aqoonsiga kansarka (P) ee ku saleysan ΔA650/525 sida soo socota.

halka b=5.3533,w1=-6.965. Kala soocida muunada, itimaalka wax ka yar 0.5 ayaa tilmaamaya muunad caadi ah, halka suurtogalnimada 0.5 ama ka badan ay muujinayso muunada kansarka. Jaantuska 2c waxa uu muujinayaa jaantuska jaahwareerka ah ee ka dhashay ansaxinta ka tagitaanka, kaas oo loo isticmaalay in lagu ansixiyo xasiloonida habka kala soocida. Jaantuska 2d waxa uu soo koobayaa qiimaynta baadhista ogaanshaha ee habka, oo ay ku jiraan dareenka, gaar ahaan, qiimaha saadaasha togan (PPV) iyo qiimaha saadaasha xun (NPV).

Biosensors-ku-saleysan taleefanka casriga

Si loo sii fududeeyo tijaabada muunada iyada oo aan la isticmaalin spectrophotometers, cilmi-baarayaashu waxay adeegsadeen sirdoonka macmal (AI) si ay u tarjumaan midabka xalka oo ay u kala saaraan shakhsiyaadka caadiga ah iyo kuwa kansarka leh. Marka la eego tan, aragtida kombuyuutarka ayaa loo isticmaalay in lagu turjumo midabka Cyst/AuNPs DNA-ga caadiga ah (guduud) ama DNA-da kansar ah (casaan) iyadoo la adeegsanayo sawirada 96-ceel oo taarikada ah oo lagu qaaday kamaradda taleefanka gacanta. Sirdoon macmal ah ayaa yarayn kara kharashaadka oo wanaajin kara marin u helka tarjumaadda midabka xalalka nanoparticle, iyo iyada oo aan la isticmaalin wax qalab casriga ah ee casriga ah. Ugu dambeyntii, laba nooc oo mashiinka wax lagu barto, oo ay ku jiraan Random Forest (RF) iyo Support Vector Machine (SVM) ayaa loo tababaray si ay u dhisaan moodooyinka. Labada nooc ee RF iyo SVM waxay si sax ah u kala saareen shaybaarada kuwo togan iyo kuwo taban oo sax ah 90.0%. Tani waxay soo jeedinaysaa in isticmaalka garaadka macmalka ah ee biosensing-ku-saleysan taleefoonka gacanta ay suurtagal tahay.

Jaantuska 3. (a) Heerka bartilmaameedka ee xalka la duubay inta lagu jiro diyaarinta muunada ee tallaabada helitaanka sawirka. (b) Tusaalaha sawirka la qaaday intii lagu jiray tallabada soo iibsiga sawirka. (c) xoojinta midabka ee xalalka cyst/AuNPs ee ceel kasta oo saxan 96-ceed ah oo laga soo saaray sawirka (b).

Isticmaalka Cyst/AuNPs, cilmi-baarayaashu waxay si guul leh u horumariyeen dareemi fudud oo loogu talagalay ogaanshaha muuqaalka muuqaalka methylation iyo dareeme awood u leh inuu kala saaro DNA-da caadiga ah ee DNA-da kansarka marka la isticmaalayo muunadaha dhiigga ee dhabta ah ee baaritaanka leukemia. Dareemka la sameeyay ayaa muujiyay in DNA-da laga soo saaray shaybaarada dhiigga dhabta ah ay awood u leedahay in ay si degdeg ah oo kharash-ku-ool ah u ogaato qadar yar oo DNA ah oo kansar ah (3nM) bukaannada leukemia 15 daqiiqo gudahood, waxayna muujisay saxnaanta 95.3%. Si loo sii fududeeyo shaybaarka muunada iyadoo meesha laga saarayo baahida loo qabo spectrophotometer, barashada mashiinka waxaa loo isticmaalay in lagu tarjumo midabka xalka iyo kala soocida shakhsiyaadka caadiga ah iyo kuwa kansarka leh iyadoo la adeegsanayo sawirka taleefanka gacanta, saxsanaanta sidoo kale waxaa lagu guuleystey 90.0%.

Tixraac: DOI: 10.1039/d2ra05725e